Quinamine

Quinamine, CjgH240jN2. This alkaloid was isolated from Cinchona succiruhra bark by Hesse and subsequently found by him in the barks of several cinchona spp. but especially in C. ledgeriana bark. It has been examined in detail recently by Henry, Kirby and Shaw. )... 

According to Hesse, conquinamine, an isomeride of quinamine (see table below) jdelds, on appropriate treatment, quinamicine and apoquin-amine. Raymond-Hamet has shown that cinchonamine (below) and aricine (table, p. 466) give indole colour reactions and in that respect resemble quinamine. 

Quebracho alkaloids, 500, 511 Quinamicine, 465 Quinamine, 419, 463 apoQuinamine, 465 C inazoline group alkaloids, 617 Quinenine (quinene), 438, 439, 440 apoQuinenine, 440 Quinetum, 420... 

Similar removal of an alcoholic substituent is found in the indophenol color reaction of p-hydroxybenzyl alcohols (XXXIX) with TV-chloro-quinoneimide (Ziegler and Gartler (42, 43), Gierer (20)). If the quinamine type compound (XL) is assumed as an intermediate in this reaction, its decomposition to the indophenol (XLI) and the aldehyde (XLII) (42, 43) would be analogous to the decomposition of XXXII postulated above. 

Aminotropones have been reported through a single-step cyclization-ring expansion process from 4-aminocyclohexa-2,5-dienones (p-quinamines) bearing a 4-sulfinyl or 4-sulfonyl methyl group on reaction with sodium hydride (Scheme 62).97... 

Recent extractions440 of the leaves of Cinchona ledgeriana have resulted in the isolation of quinamine (previously observed), 3-ep/-quinamine, aricine, and a new alkaloid which may prove to be stereoisomeric with quinamine. 11-Hydroxy-pleiocarpamine occurs in Vinca erecta 4b and herbacine and herbaine in V. herbacea.44c Yohimbine appears to be the major alkaloid of the trunk bark of Pausinystalia macroceras, in which it occurs with four other alkaloids of this group.44d Pleiocarpamine occurs in association with nine alkaloids of the aspidospermine-eburnamine group in the stem and root bark of Hunteria elliottii (Stapf.) Pichon.44e... 

There are recognized at present three naturally occurring members of this group, cinchonamine, quinamine, and conquinamine, all minor alkaloids of certain Cinchona and Memijia species. The elucidation of their structures led to the suggestion that the quinoline moiety of the major bases, e.g., cinchonine and quinine, of these plants was probably derived from tryptophan via an indolic precursor. It has since been demonstrated from the results of feeding experiments with isotopically labeled tryptophan that this amino acid really can serve as a precursor of various indole alkaloids (1) as well as of quinine (2). The details of these processes are not yet known but probably involve an intermediate(s) related to cinchonamine (2, 3, 6). 

Early work had shown cinchonamine to give color reactions typical of indole alkaloids (7), and this was also evident from its UV-spectrum (8). The base differs from the major cinchona alkaloids in yielding, upon oxidation with chromic acid (6), 3-vinylquinuclidine-8-carboxylic acid (III), mp 209°, [a]D — 29° (CHCI3), which was first obtained from quinamine (9). The nature of the remainder of the molecule followed from the conversion of cinchonamine into 0,iVb-diacetylallocinchon-amine (I), mp 159°, [a]D — 7° (CHCI3), by refluxing acetic anhydride and its subsequent oxidation to 3-/3-acetoxyethylindole-2-aldehyde (H) (6). 

Final clarification of the structure of quinamine was accomplished on the one hand by the production of cinchonamine upon lithium aluminum hydride reduction of the base (6), and on the other hand by the reverse reaction brought about by peracid (18) (Chart I). The reduction is explicable via the ring chain tautomeric hydroxyindolenine (VIII), which is also the primary product of the peracid oxidation of cinchonamine [cf. oxidation of tetrahydrocarbazole (19)]. The oxidation is stereospecific, but the stereochemistry of the introduced C-7 hydroxyl is still unknown. 

With the structure of quinamine firmly established, its other reactions can now be considered (Chart II), all of which proceed via VIII. When the alkaloid was refluxed with acetic anhydride or acetyl chloride, acetyl-apoquinamine (O-acetyl-d3- 14-cinchonamine, XII), picrate, mp 143° was obtained. The change may be formulated, quinamine VIII-XII, with the last step being a special case of a general reaction of hydroxy-indolenines (20). The analogous transformation can be realized very easily when 7-hydroxy-7/f-yohimbine methiodide (X) is boiled in methanol (21). 

Prolonged reflux of either quinamine or apoquinamine, mp 115°, [a]D — 32.9° (0.1 N H2SO4), in dilute acetic acid gave an amorphous material called quinamicine (14, 15), to which structure XIV was given (16). 

It was shown later (23) that quinamicine was in reality crude quin-amidine (XIV), mp 93° (ethanolate), which Hesse (14) had prepared in a pure state either by allowing quinamine to stand at room temperature for several days in 13% hydrochloric acid or by heating the alkaloid at 130° in aqueous tartaric acid. 

Lithium aluminum hydride reduction of epiquinamine, as expected, afforded 3-epicinchonamine, mp 168°, [a]D +48° (EtOH), also obtainable along with cinchonamine by the sodium-ethanol reduction of apoquinamine (23). Finally, it was shown in 1945 that, on heating quinamine or dihydroquinamine above its melting point, formaldehyde was evolved, and this was taken as evidence for the presence of a 2-hydroxymethyl on an indole a-carbon (15). In the light of the true structure, the writer would like to suggest that this aldehyde is formed by pyrolysis of a 1,3-glycol, that is, a retro Prins reaction (25). 

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